Nutritional Geometry 2: Carb Restriction

Last week’s focus was the evidence in favor of a low-protein diet.  In this context, high-carb diets came out on top.  But there is also evidence that for the average denizen of the developed world who does not restrict protein, there are dangers in a diet based on staple carbohydrates, especially sugars and simple starches that pass quickly from the stomach to raise blood sugar.

Beginning in the 1970s, health literature convinced Americans to avoid fatty foods, and the processed food industry was eager to oblige, advertising “low fat”, while adding more sugar to make foods tasty, and taking advantage of a new, efficient chemical process that made high-fructose corn syrup cheaper than sugar.  But as we substituted carbs for fat, we became obese and diabetic.  Metabolic syndrome and Type 2 diabetes were new terms added to the medical lexicon to describe what was ailing us.  Gary Taubes was first to hypothesize a causal relationship:  Our high-carb diet was leading to insulin resistance (which promotes weight gain) and weight gain (which promotes insulin resistance)—a vicious cycle that he first wrote about in the 1990s.

  • Diets that are high in fat, low in carbs, are an effective way to lose weight, at least in the short term.  Herman Taller, Robert Atkins, and Barry Sears taught this truth to three successive generations of Americans.
  • In animal experiments, insulin and its cousin IGF-1 are the hormones that mediate the connection between more food and shorter life.
  • Blood sugar levels rise with age, and in people with genes for exceptional longevity, the rise happens more slowly.  Blood sugar levels are a risk factor for mortality.  So how much of a stretch is it, really, to say that the rise in blood sugar with age contributes to risk for the diseases of old age?


The case against carbohydrates comes right out of mainstream practice for diabetes, but it has also been treated as a fringe fad when David Perlmutter stretched the case to make a point in a series of bestselling books.  In Grain Brain, Perlmutter pounds home the association between high blood sugar and all the diseases of old age, but most especially dementia.  (Vascular dementia to a greater extent than Alzheimer’s disease.)

The combination of biochemistry with population data associating carb intake with metabolic syndrome has convinced many people that a carbohydrate-based diet is a hazzard.  But it’s a difficult case to prove, because humans don’t take well to living in cages, and because epidemiological studies of human aging require decades.  In reading this week, I’ve discovered just how contentious is the whole subject of low-carb vs low-fat diets. Many such deeply divisive questions about health can be traced to corporate interests on one side, but this one may be academic, with ambiguous data, no long-term results, and different individual responses that are seen through different theoretical lenses.

Although bottom-line questions about mortality and life expectancy may be difficult to address in human studies, we might hope for an answer to the question: Do people whose diets have a lower glycemic index have a lower risk of metabolic syndrome?  The best study I’ve been able to find on this question [2004] associates insulin resistance with dietary factors in 2,800 sons and daughters of the original Framingham heart study.

After adjustment for potential confounding variables, intakes of total dietary fiber, cereal fiber, fruit fiber, and whole grains were inversely associated, whereas glycemic index and glycemic load were positively associated with [insulin resistance]. The prevalence of metabolic syndrome was significantly lower among those in the highest quintile of cereal fiber and whole-grain intakes relative to those in the lowest quintile category after adjustment for confounding lifestyle and dietary factors. Conversely, the prevalence of metabolic syndrome was significantly higher among individuals in the highest relative to the lowest quintile category of glycemic index.

Fruits and whole grains were found to provide protection against insulin resistance, despite the fact that they are primary carb sources.  Presumably, it is only sugar and simple carbs (white flour, rice, potatoes) that add to risk of insulin resistance.

A South African doctor collected stories from patients who, by and large, were very satisfied with the results of switching to a low-carb, high-fat diet. Almost all lost weight.  Some claimed that their diabetes was “cured”.

In this study, people lost weight on a six-month program of either restricted fat or restricted carbs.  But people who were already insulin-resistant did a little better on the low carb diet, while those who still retained insulin sensitivity lost more on the low fat diet.

This study put obese subjects with metabolic syndrome on either a low-fat or low-carb diet for six months.  Both groups lost weight and gained insulin sensitivity, on average.  The low-carb group lost more weight and gained more insulin sensitivity.  However, there was a lot of variation within the groups.

Insulin resistance is associated with diabetes and heart disease, both independently and as part of metabolic syndrome. Exercise has a strong beneficial effect and obesity a strong adverse effect. The balance of evidence suggests that a high-fat diet is likely to reduce insulin sensitivity but the effects of dietary carbohydrates are more controversial. Extensive studies in animals showed a detrimental effect of diets very high in fructose or sucrose, particularly in association with induction of hypertriglyceridemia. The more limited studies in humans had conflicting results, partly because of heterogeneity of design. Certain groups of subjects may be more sensitive to adverse effects of high intakes of dietary sucrose or fructose. [ref]

In other words, “There is conflicting evidence concerning the influence of total carbohydrate intake on insulin sensitivity.”

Two NIH studies [one, two] by Kevin Hall just this year compared short-term effects on metabolism from carb and fat restriction.  They put people in metabolic chambers to measure CO2 and H2O in their respiration, in order to calculate how much fat was being burned.  Hall claims that the results disprove the insulin theory of weight loss.  But to me the results seem puzzling and inconclusive.  They claim to calculate that the short-term weight loss from carb restriction is loss of muscle, not fat.  This is disturbing, if true.  The metabolic calculations are based on isotope labeling and other sophisticated technologies.  I trust the chemistry, but I tend to skepticism based on the fact that once in the body, labeled water gets mixed to an unknown extent with ubiquitous body water.  Short-term studies with sophisticated metabolomic measurements might tell us a good deal about the body’s biochemistry, but still leave us wondering about long-term accommodations of hormonal balance, energy metabolism, and gut biota.

Past positive results from low-carb diets, Hall says, are probably about “compliance” and not metabolism.  “Compliance” is our ability to stick with a diet, and, IMHO, this should not be separated out as some kind of soft, psychological confounder.  It may well be that the whole advantage of a high fat diet is that those people for whom it works—not everyone—feel less hunger and more sustained energy, and that may well be linked to insulin cycling.

What can we conclude but that we’re each on our own, and we have to find the diet that works best for us as individuals?  And that that our dietary needs may change with age, so repeating the self-experimentation at least once a decade is helpful.  In experimenting on yourself, keeping weight off is probably as good a measure as any of how well your body is responding.
Glycemic index and glycemic load

Glycemic index is about how quickly the carbohydrates in a particular food enter the bloodstream.  Glycemic load also takes into account how much carbohydrate the food contains, and also a guess at portion size.  Here’s a chart from Harvard Med School with glycemic index and glycemic loads for 100 “common foods” (some more common than others).  Much of the chart is predictable—cakes and sodas look bad, beans and nuts look good.  There are a few good surprises, and a few bad ones.  (Note that the GL listed for oranges =45 is almost certainly a mistake.  It should be 5 or 6.)

Good Surprises         GL Bad Surprises              GL
Premium Ice Cream 3 Cornflakes 20
Watermelon 4 Ocean Spray Cranberry Juice 24`
Apple 4 Pasta 26
Peanut M&Ms 7 Raisins 28
Whole Wheat bread 8 Baked potato 33
Regular ice cream 9

The ranking by glycemic load is appropriate if you are trying to minimize total insulin burden.  But if you are aiming for a low-protein, high-carb diet as described last week, then you are interested in glycemic index (because you want high-carb foods that don’t trigger insulin release).  The catch (for protein restricters) is that most foods with low GI are protein sources.  Which foods offer a combination of low protein and high carb without the insulin trigger?  Grapefruit stands out, apples, pears and other fruits will be preferred carb sources.  Some kinds of brown rice are more equal than others, while potatoes will be avoided because of too high a GI, while whole wheat and corn will be taken in moderation because they have too much protein.


Fructose, Glucose, Sucrose

So lotsa fruit seems to be the answer…until we introduce one more wrinkle.  Fruit contains fructose, and there is a school of thought that says fructose is much worse for you than glucose.

There are two simple 6-carbon sugars, fructose and glucose, and table sugar=sucrose is a loose binding of one fructose with one glucose.

Fructose and glucose are both sweet, and they’re often found together in fruits.  Apples and pears have a lot more fructose than glucose, while bananas, peaches and sweet potatoes have a little more glucose than fructose.  Honey has more fructose than table sugar.

Starch is a polymer of glucose.  It is quickly broken down (beginning in the mouth) into glucose molecules, so starchy foods have a high glycemic index.  But starch is all glucose, no fructose.


Glucose and fructose may be chemical cousins, but the body treats them quite differently in the short term.

  • Glucose is fuel, usable right away.  When you eat enough for your activity level, glucose is absorbed right into the blood, and it is consumed promptly.  When you eat more glucose than you can burn, insulin is secreted, signaling the liver to remove some glucose and turn it to glycogen.  The liver stores about a day’s supply of glycogen to be drawn on as necessary, and glucose in excess of that is turned to triglycerides, a form convenient for storing energy in fat cells.
  • Fructose is also absorbed promptly from the stomach into the bloodstream, but it is removed immediately by the liver, turned directly to triglycerides.  No insulin is involved.

The short-term metabolism of fructose and glucose is well characterized, but you and I are interested in the long-term consequences of eating fruits high in fructose compared to starches which are quickly metabolized to glucose.  This turns out to be a controversial topic.

In recent years, Robert Lustig and Richard Johnson have argued that foods with more fructose than glucose lead quickly to insulin resistance.  They blame soaring rates of obesity and metabolic syndrome=type 2 diabetes on the invention of a process for producing sugar from corn starch that is cheaper than cane sugar.  The “high-fructose corn syrup” that results happens to be 55% fructose.

Yes, fructose has a low glycaemic index of 19, because it doesn’t increase blood glucose. It’s fructose, for goodness sake. It increases blood fructose, which is way worse. Fructose causes seven times as much cell damage as does glucose, because it binds to cellular proteins seven times faster; and it releases 100 times the number of oxygen radicals (such as hydrogen peroxide, which kills everything in sight). Indeed, a 20oz soda results in a serum fructose concentration of six micromolar, enough to do major arterial and pancreatic damage. Glycaemic index is a canard; and fructose makes it so. Because fructose’s poisonous effects have nothing to do with glycaemic index; they are beyond glycaemic index. [Lustig writing in The Guardian]

I’m not so impressed with the “seven times faster”, because fructose doesn’t remain long in the bloodstream, and I’m not so concerned about free radicals because (as I’ve written) they are as likely to increase our life expectancy as to decrease it.  Lustig also writes that because fructose tastes so good and bypasses insulin and blood sugar, it undermines the satiety response and leads to compulsive eating.  But the most complelling claim here is about the loss of insulin sensitivity, which I regard as a hallmark of aging.  Is fructose really worse for insulin resistance than glucose?  Lustig says YES, and his theory is articulated here.  Lustig makes his case by reasoning about biochemistry in the liver.  But what about real evidence in real people?  In short-term studies, substitution of fructose for glucose in the diet shows no sign of increasing insulin resistance; on the other hand, there is a well-known correlation between consumption of high-fructose corn syrup with metabolic disease.

What Lustig comes to beneath the headlines is, “the dose makes the poison”; and I think this is a healthy attitude for all of us.  Drinking sugared beverages and eating (more than occasionally) foods sweetened with high-fructose corn syrup damages insulin sensitivity.  At the other end, eating a few pieces of fruit during the day can be part of many diet plans that work well for health and longevity.  Those are the easy cases.  In between we have the more difficult case of the semi-fructarian.  That would be me.  I get most of my carbs from fruit, and I avoid starch (rice, potatoes, bread, pasta).  I maintain weight with exercise and portion control, I eat leafy greens every day and I get a ton of fiber, and though my protein intake is high compared to last week’s ideal (~60g/day), it’s all vegetable protein.  Would I be better off if I backed off from my fruit consumption and substituted whole wheat bread and other complex carbohydrates?  It’s an experiment that I might try next winter—but not in September when every kind of delicious fruit is fresh and abundant.

In any case, there is a consensus view that moderate fructose is part of a healthy diet, and that excessive fructose exacerbates the ill effects of a sugary diet [ref, ref, ref, ref, ref, ref, ref].  After reading all these articles (well…reading all the abstracts and some of the content underneath), I’m not convinced one way or the other about fruits (glucose+fructose) vs grains (glucose only, from starch).


Insulin resistance is tied to high blood sugar

Metabolic syndrome, including the “normal” version that comes with aging, is characterized by failure to respond to insulin, leading to both higher insulin levels and higher blood sugar.  Is it the higher insulin level or the higher blood sugar that is responsible for the damage?  YES.

Insulin signaling speeds up the rate of aging.  Sugar in the blood reacts with proteins to create cross links (glycation) that prevents the protein from folding properly.  (Fructose is more prone to this reaction than glucose, but fructose does not stay in the blood so long.)  Type I diabetics have no insulin, and if their insulin injections are not carefully regulated, they are at risk for blindness and nerve damage in the extremities, both from high blood sugar.  So, with metabolic syndrome, both the insulin levels and high blood sugar pose risks.  The proper medical terminology for this situation is “double whammy”.

So both high insulin and high blood sugar are bad for us.  With the separation of fructose from glucose, we have the possibility of coupling lower insulin levels with higher blood sugar. Is the tradeoff worthwhile? Is fructose the optimal low glycemic index sweetener?

And in the end…

You have every right to ask where I’m going to come down on these questions after a post that is longer and fuller of ambiguities than the usual.  I’m going to disappoint you. It’s clear to me

  • that excessive sugar, both glucose and fructose, is bad for most everyone
  • that high fiber is good in a lot of ways
  • that different metabolisms respond differently to low-carb and low-fat diets.
  • that weight control is a good way to tell if a diet is working for you

It leaves me counseling personal experimentation, which is what I always say anyway.

There is a phenomenal amount of individual variability in energy expenditure, both resting and total.   Measured across two weeks, one person had total EE  almost 800 cal/day above their baseline while another had a EE almost 1200 cal/day below baseline.  That’s huge.  I imagine that the individual whose resting EE declined by almost 500 cal/day will be having a tougher time maintaining his/her weight loss than those lucky few who saw increases. [from a pro-carb blogger]


A simple program for weight loss and life extension

Before each time that you eat, do 1 to 2 minutes of exercise, intense enough to leave you panting and drink a pint of water.  The result is to suppress the sugar and insulin spikes that follow a meal, and to burn more of the food energy, store less as fat.

Next week, part 3: Specifics on the high-fat, ketogenic diet

Nutritional Geometry

We all know that the less we eat, the longer we live, and that periods of fasting, long and short, can also trigger a longevity dividend. What about macronutrient proportionsprotein, carbohydrates, and fat? The argument for carb restriction is that it helps keep insulin signaling down, and slows the inevitable advance of metabolic syndrome. The argument for protein restriction is that animals on protein restricted diets have sometimes been found to live longer, independent of total calorie intake. The argument for fat restriction is that mice on a high-fat diet have shortened lifespans compared to either high-carb or high-protein. So, what macronutrient proportions are best for people, or does it matter at all? I have advocated the carb restriction diet in the past, but today I’m considering the evidence for protein restriction, and speculating on the possibility we might be able to do both.

Nutritional Geometry is a 9-year-old Australian approach to macronutrient proportions which has been honing its message more recently [ref, ref, ref]. The topic has provided fodder for research grants (and for bloggers) because it is rich with nuance and resists generalization.

If you are looking for bottom-line advice, I’d say:

  • High-fluid, high fiber content are consistent recommendationsno tradeoffs, no qualifications. Leafy greens rule!
  • Low-protein when you’re young, higher protein when you’re old
  • Vegetable protein is preferable to meat or dairy
  • If you’re game to try something new, a high-fat ketogenic diet may offer advantages.

But the subtleties are interesting and worth exploring, and (as always) the best diet for you is the one you can live with.

Last year, the Australian group published a study in which they fed mice on 25 different diets, differing in protein, fat, carbohydrate, and energy density. The main result from this study is that mice fed a low protein, high carb diet lived longest, though they ate more food—presumably because they sensed that they were not getting enough protein. At the lowest protein concentrations, their total protein was still low, even though they ate more food, and they lived longer, even though they ate more food. For mice, a low-protein chow led to more eating and a longer life. The trick worked for low protein, high carb diets but not for low protein, high fat diets. In this case, the mice ate so much more food that they became obese and their lifespans were shorter. The optimum diet for female mice had an 11:1 ratio of carbohydrate to protein, and for male mice, 13:1.

If we extrapolate to humans, the message would be that for people who prefer not to restrict their portions, a very low protein diet provides a path to a longer life. But this is a dubious extrapolation. The mice were given no choice of chow. (There were 25 different formulations, but only one available to each cage of mice.)  People, in contrast, have a dizzying choice of foods. I know the feeling of having had my fill of fruit, and though not feeling really hungry, craving protein nevertheless. Humans are not at all comparable to lab mice in this regard.

A balanced diet?

A balanced diet?

I wonder for how many people a diet restricted to foods that have carb:protein ~ 12 to 1 is realistic. Here is a list of foods with carb:protein ratios [from USDA web site]:

protein2carb-ratiosConclusion: To get the low protein diet of the mouse experiment, you’d probably have to be a fructarian.

I was surprised to see that the study reported no benefit from a high-fiber diet.

Reduction in calorie intake was achieved by diluting the food with nondigestible cellulose, which allows ad libitum feeding but restricts total energy intake when compensation for dilution by increasing food intake is incomplete. Mice fed experimental diets containing 50% nondigestible cellulose ate a greater bulk of food (3.6 vs 2.5 g/day) but ingested about 30% less total energy than mice provided with food containing higher energy content (30 vs 42 kJ/day). Therefore, these mice had a reduction in energy intake similar to those reported in nearly all other studies of calorie restriction in which access to food was restricted… When corrected for lean body mass, the hazard ratio for death was not influenced by calorie intake, except at the highest energy intakes, which were achieved only by low-protein, high-fat diets.

Fiber in the chow filled the mice up, causing them to eat less calories (though more bulk) than they would have otherwise. But did they live longer? Yes, they did, though you might not get it from the language used here. Lifespan was not increased by lower calories “when corrected for lean body mass”, but whem mice are on a lifelong low-calorie diet, they don’t grow as large, so their lean body mass is smaller. Correction “for lean body mass” is generally not the way data is reported in these experiments. So the result here is not necessarily inconsistent with the great body of experimental results that say lifelong caloric restriction leads to longer lifespan.

Most interesting is the last caveat: The problem with high fat diets is that mice overeat, become obese and have shortened lifespans. But with both high fiber and high fat, the mice tended not to overeat, and their lifespans were enhanced.

This may suggest a practical diet strategy for humans. Mice on a high-fat diet ate a lot more calories, and similarly some people find deep fried foods and milk shakes tempt them to eat too much. But for those with the willpower to interrupt a high-fat meal, they may find that they don’t get hungry for several hours afterward. This is because fat is slower to be digested than either protein or (especially) carb. High-carb meals lead to a fast rise in blood sugar, then an insulin spike that makes blood sugar plummet, triggering hunger. After a high-fat meal, hunger is much slower to return.

High-fat meals lead mice to obesity and short lifespans because they overeat. Extra fiber in the food helps them to regulate their intake. If this works for humans, there is the possibility that a high-fat, high-fiber diet can offer the advantages of both protein restriction and low insulin. I’ll go into this option in depth next week.
Protein: How low can you go?

The biggest issue is maintaining muscle mass, which is crucial to vitality and wellbeing, and becomes a protective factor from mortality as we get older. We have all seen pictures of starving African children with bloated bellies. They are not actually suffering from insufficient calories, but insufficient protein. Their largest muscle, in the abdomen, has beeen deprived of protein so long it has lost all its tone.

Both Pederson and Rand (2013) recommend about 0.85g protein for each Kg of body weight. For a 160-pound man that’s 61g, and for a 125-pound woman, 47g of protein daily. Pederson found that all the diseases of old age are statistically associated with higher protein intake. More general sources quote a slightly lower 0.8g/Kg.

These numbers are only an average over many populations in many studies. Your body might need a lot more or a lot less protein than this, and your best indication is to monitor your energy level, your weight, your muscle mass, and blood analysis as you experiment with different diets.

In this study [2007] of Swedish women 30-49, those in the highest decile of protein consumption died at a rate 20% higher than those with the lowest decile. But mortality rates are low through that age range, and what is more important is the effect on health and mortality in the long term.


Animal vs vegetable protein

In a literature review, Pederson (2013) found links between animal protein intake and various mortality factors, but vegetable protein was either beneficial or neutral. Surprisingly, it is the high-protein diets that are associated with type-2 diabetes, not the high-carb diets. But this conclusion seems limited to animal sources.

This study [2012] from Harvard School of Public Health found a 13% increase in mortality for every daily meal at which red meat was consumed, rising to 20% for processed meats, corresponding to 2 to 3 years of extra life.

Seventh Day Adventists are, as a group, health- and diet-conscious, and they live longer. Their religion tells them not to eat meat, but many do anyway. Seventh Day Adventists who are vegetarian live 3 years longer than Seventh Day Adventists who eat meat.

How does the body know animal from vegetable protein? I have seen no theories on this. Animal protein is generally higher in methionine, but methionine restriction only lowers mortality when methionine intake is very low–probably not the case generally in any of these studies. It could be the saturated fat that accompanies the protein; or it could be hormones that are present in all animals, with higher levels in commercial meat; or it could be an effect mediated through the effect on intestinal flora. But my best guess is that it has to do with heightened inflammation from a low-level immune response to chronic exposure to alien animal proteins.


More protein as you get older

My favorite authority on this and other questions of diet is Valter Longo and his group at University of Southern California. In their 2014 review, they found a dividing line at age 65. Younger than 65, higher protein intake was associated with higher mortality, and older than 65, higher protein intake was associated with lower mortality. As in other studies, the damage was only visible for animal protein, and disappeared into the noise for vegetable protein.

Frailty is an issue in older adults., and greater muscle mass can support a more vigorous exercise regimen. This is a plausible reason for the increased protein need with advanced age. Longo also talks about IGF-1 signaling. IGF stands for “insulin-like growth factor”, and it is a hormone we need when we are young, but which increases mortality when we are older. Lower protein is associated with lower IGF-1, though the statistical association falls short of suggesting that this is the reason that low protein is beneficial.

This is the best article I have found on the subject of increasing protein need with age, but still it is not really what I’d like to see. Mortality in young people is not the best measure of whether a low protein diet is beneficial, because mortality in young people is still low, and even a temporary doubling of mortality make little difference. What we really want to know is how protein in the diet of young people affects their life expectancy when they get older. This is a study that has not yet been done, probably because it involves following a large population for a long period of time (like the Framingham Heart Study and the Whitehall Study in Britain, but these did not address protein.)
Roughage = Dietary Fiber

Everyone agrees that fiber in the diet has a large benefit for gut health and especially for preventing colorectal cancer. I have speculated that the benefit goes beyond this. A high-fiber diet is a calorie restriction program in itself. Fill your belly with fiber, and it you feel full with fewer calories. An ultra-high fiber diet pushes food through your digestive tract faster, so you absorb less of it. Fat is adsorbed on the fiber, and less of it makes it into your metabolism. High fiber in the gut encourages a microbial ecology that affords you less calories.

I speculate based on personal experience, but there is also some literature touching on the subject [ref, ref, ref]. “There was a considerable variability in digestibility of fiber components between individuals.”

Does fiber prevent the absorption of vitamins and other micronutrients as well? Maybe. I haven’t seen literature on the topic, but it makes sense that cellulose adsorbs a variety of molecules that are carried through the intestine undigested. Best to take your supplements separate from your fiber.

I am out on a limb recommending an ultra-high-fiber diet, and I suspect that results will vary widely among individuals. But what is not controversial is the health value of leafy green vegetables—the more the merrier.

Conclusions so far:

This much is clear: Green vegetables are good.  Animal protein is bad.

Beyond that, we might be tempted to interpret the Nutritional Geometry literature to say that “carbs are ok”.  I am wary of this conclusion, however.  It’s not just the standard warning that “mice are not people”. The benefits of a high-carb diet have only been shown in the context of severe protein restriction that I think is unrealistic for most of us. To be continued…

Next week: Metabolic Syndrome, Glycemic Load and The ketogenic Diet